TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23407	70444;70445;70446	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
N2AB	21766	65521;65522;65523	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
N2A	20839	62740;62741;62742	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
N2B	14342	43249;43250;43251	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
Novex-1	14467	43624;43625;43626	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
Novex-2	14534	43825;43826;43827	chr2:178575913;178575912;178575911	chr2:179440640;179440639;179440638
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-129
• Domain position: 63
• Structural Position: 146
• Q(SASA): 0.9056
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/K	rs1417805989	0.303	0.025	N	0.387	0.14	0.208000267992	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/K	rs1417805989	0.303	0.025	N	0.387	0.14	0.208000267992	gnomAD-4.0.0	3.18337E-06	None	None	None	None	I	None	0	4.57331E-05	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.9776	likely_pathogenic	0.9887	pathogenic	-0.041	Destabilizing	0.845	D	0.599	neutral	None	None	None	None	I
R/C	0.7965	likely_pathogenic	0.8961	pathogenic	-0.198	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
R/D	0.9975	likely_pathogenic	0.998	pathogenic	-0.06	Destabilizing	0.975	D	0.598	neutral	None	None	None	None	I
R/E	0.9743	likely_pathogenic	0.9816	pathogenic	0.025	Stabilizing	0.845	D	0.594	neutral	None	None	None	None	I
R/F	0.9916	likely_pathogenic	0.9954	pathogenic	-0.227	Destabilizing	0.996	D	0.635	neutral	None	None	None	None	I
R/G	0.9757	likely_pathogenic	0.9879	pathogenic	-0.255	Destabilizing	0.892	D	0.517	neutral	N	0.482065256	None	None	I
R/H	0.6008	likely_pathogenic	0.7062	pathogenic	-0.902	Destabilizing	0.987	D	0.617	neutral	None	None	None	None	I
R/I	0.9377	likely_pathogenic	0.9648	pathogenic	0.495	Stabilizing	0.983	D	0.64	neutral	N	0.476189452	None	None	I
R/K	0.3901	ambiguous	0.49	ambiguous	-0.083	Destabilizing	0.025	N	0.387	neutral	N	0.485568589	None	None	I
R/L	0.9328	likely_pathogenic	0.9609	pathogenic	0.495	Stabilizing	0.916	D	0.517	neutral	None	None	None	None	I
R/M	0.9682	likely_pathogenic	0.9834	pathogenic	-0.025	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	I
R/N	0.9916	likely_pathogenic	0.9943	pathogenic	0.086	Stabilizing	0.975	D	0.579	neutral	None	None	None	None	I
R/P	0.9892	likely_pathogenic	0.993	pathogenic	0.337	Stabilizing	0.987	D	0.607	neutral	None	None	None	None	I
R/Q	0.629	likely_pathogenic	0.74	pathogenic	0.045	Stabilizing	0.975	D	0.582	neutral	None	None	None	None	I
R/S	0.9897	likely_pathogenic	0.9944	pathogenic	-0.253	Destabilizing	0.892	D	0.592	neutral	N	0.466972741	None	None	I
R/T	0.9782	likely_pathogenic	0.988	pathogenic	-0.02	Destabilizing	0.967	D	0.563	neutral	N	0.466972741	None	None	I
R/V	0.9628	likely_pathogenic	0.9801	pathogenic	0.337	Stabilizing	0.975	D	0.646	neutral	None	None	None	None	I
R/W	0.9034	likely_pathogenic	0.9364	pathogenic	-0.291	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
R/Y	0.9628	likely_pathogenic	0.9773	pathogenic	0.122	Stabilizing	0.996	D	0.607	neutral	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.